668991-40-0

Upstream product

• 89-98-5 2-chloro-benzaldehyde 
• 21854-95-5 2,2'-dichlorobenzil 
• 71776-58-4 (1R,2S)-1,2-bis-(2-chloro-phenyl)-ethane-1,2-diol 

Relevant academic research and scientific papers

Chiral Benzoins via Asymmetric Transfer Hemihydrogenation of Benzils: The Detail that Matters

The synthesis of enantiomerically pure benzoins by hydrogenation of readily available benzils has been long thwarted by their base-sensitivity. We show here that an iron(II) hydride complex catalyzes the asymmetric transfer hydrogenation of benzils from 2-propanol. When strictly base-free conditions are granted, excellent enantioselectivity is achieved even with o-substituted substrates, which are particularly challenging to prepare with other methods. Hence, under optimized reaction conditions, chiral benzoins were prepared in good yields (up to 83%) and excellent enantioselectivity (up to 98% ee) in short reaction times (30-75 min). Also, this work confirms that both enantiomers of the benzoin products can be accessed when a metal catalyst is used, which is a clear advantage over enzymatic methods.

Two enantiocomplementary ephedrine dehydrogenases from arthrobacter sp. TS-15 with broad substrate specificity

The recently identified pseudoephedrine and ephedrine dehydrogenases (PseDH and EDH, respectively) from Arthrobacter sp. TS-15 are NADH-dependent members of the oxidoreductase superfamily of short-chain dehydrogenases/reductases (SDRs). They are specific for the enantioselective oxidation of (+)-(S) N-(pseudo)ephedrine and (-)-(R) N-(pseudo)ephedrine, respectively. Anti-Prelog stereospecific PseDH and Prelog-specific EDH catalyze the regio- A nd enantiospecific reduction of 1-phenyl-1,2-propanedione to (S)-phenylacetylcarbinol and (R)-phenylacetylcarbinol with full conversion and enantiomeric excess of >99%. Moreover, they perform the reduction of a wide range of aryl-aliphatic carbonyl compounds, including ketoamines, ketoesters, and haloketones, to the corresponding enantiopure alcohols. The highest stability of PseDH and EDH was determined to be at a pH range of 6.0-8.0 and 7.5-8.5, respectively. PseDH was more stable than EDH at 25 °C with half-lives of 279 and 38 h, respectively. However, EDH is more stable at 40 °C with a 2-fold greater half-life than at 25 °C. The crystal structure of the PseDH-NAD+ complex, refined to a resolution of 1.83 ?, revealed a tetrameric structure, which was confirmed by solution studies. A model of the active site in complex with NAD+ and 1-phenyl-1,2-propanedione suggested key roles for S143 and W152 in recognition of the substrate and positioning for the reduction reaction. The wide substrate spectrum of these dehydrogenases, combined with their regio- A nd enantioselectivity, suggests a high potential for the industrial production of valuable chiral compounds.

Base-Free Asymmetric Transfer Hydrogenation of 1,2-Di- and Monoketones Catalyzed by a (NH)2P2-Macrocyclic Iron(II) Hydride

The hydride isonitrile complex [FeH(CNCEt3)(1 a)]BF4 (2) containing a chiral P2(NH)2 macrocycle (1 a), in the presence of 2-propanol as hydrogen donor, catalyzes the base-free asymmetric transfer hydrogenation (ATH) of prostereogenic ketones to alcohols and the hemihydrogenation of benzils to benzoins, which contain a base-labile stereocenter. Benzoins are formed in up to 83 % isolated yield with enantioselectivity reaching 95 % ee. Ketones give the same enantioselectivity observed with the parent catalytic system [Fe(CNCEt3)2(1 a)] (3 a) that operates with added NaOtBu.

Biocatalyzed asymmetric reduction of benzils to either benzoins or hydrobenzoins: pH dependent switch

Enantiopure benzoins and hydrobenzoins are precursors of various pharmaceuticals and biologically active compounds. In addition, hydrobenzoins are precursors of chiral ligands and auxiliaries in stereoselective organic synthesis. Biocatalytic reduction of benzils is a straightforward approach to prepare these molecules. However, known methods are not selective and lead to formation of a mixture of benzoin and hydrobenzoin, requiring expensive separation procedures. Here, we describe an enzyme system Talaromyces flavus, which exhibited excellent pH dependent selectivity for the conversion of benzil to either benzoin or hydrobenzion in high ee. Thus, (S)-benzoin was the exclusive product at pH 5.0 (ee >99%), whereas at pH 7.0, (S,S)-hydrobenzoin (ee >99%, dl/meso 97 : 3) was the exclusive product. The observed pH dependent selectivity was shown to be due to the presence of multiple enzymes in Talaromyces flavus, which specifically accepted either benzil or benzoin as a substrate and exhibited different pH profiles of their activity. The biocatalyst efficiently reduced a variety of symmetrical and unsymmetrical benzils. Moreover, a 36.4 kDa benzoin reductase was purified, the N-terminal sequence of which did not show a significant similarity to any of the known reductase/dehydrogenase in the database. The protein therefore appears to be a novel reductase.

Enantioselective oxidation of 1,2-diols with quinine-derived urea organocatalyst

Quinine-derived urea has been identified as a highly efficient organocatalyst for the enantioselective oxidation of 1,2-diols using bromination reagents as the oxidant. This simple procedure utilizes readily available reagents and operates at ambient temperature to yield a wide range of α-hydroxy ketones in good yield (up to 94%) and excellent enantioselectivity (up to 95% ee).

A tailor-made chimeric thiamine diphosphate dependent enzyme for the direct asymmetric synthesis of (S)-benzoins

Thiamine diphosphate dependent enzymes are well known for catalyzing the asymmetric synthesis of chiral α-hydroxy ketones from simple prochiral substrates. The steric and chemical properties of the enzyme active site define the product spectrum. Enzymes catalyzing the carboligation of aromatic aldehydes to (S)-benzoins have not so far been identified. We were able to close this gap by constructing a chimeric enzyme, which catalyzes the synthesis of various (S)-benzoins with excellent enantiomeric excess (>99) and very good conversion. Hybrid vigor: Combining the active-site characteristics of two thiamine diphosphate (ThDP) dependent enzymes solved the long-standing problem of enzymatic asymmetric (S)-benzoin synthesis starting from commercially available benzaldehydes. The resulting rationally designed hybrid enzyme provides access to various (S)-benzoins with excellent enantiomeric excess and good conversion.

Asymmetric benzoin condensation promoted by chiral triazolium precatalyst bearing a pyridine moiety

Chiral triazolium salts bearing a pyridine ring were developed as N-heterocyclic carbene precursors. In the presence of the chiral triazolium salt and a base, the catalytic asymmetric benzoin condensation proceeded to afford the product in high level of chemical yield and enantioselectivity. A wide range of aromatic aldehydes were applicable to this reaction.

The enantioselective benzoin condensation promoted by chiral triazolium precatalysts: Stereochemical control via hydrogen bonding

The design of a new class of triazolium ion precatalysts incorporating protic substituents is described. These materials promote the enantioselective benzoin condensation of a range of aromatic aldehydes (1-62% ee). Catalyst evaluation studies strongly support the involvement of hydrogen bond donation by the catalyst in the stereocentre-forming step of the catalytic cycle.

Highly enantioselective benzoin condensation reactions involving a bifunctional protic pentafluorophenyl-substituted triazolium precatalyst

(Chemical Equation Presented) Improved catalyst design by incorporating a hydrogen bond donating substituent to improve enantiocontrol together with an acidifying pentafluorophenyl substituent to enhance catalyst efficiency results in a triazolium ion precatalyst that promotes the asymmetric archetypal benzoin condensation with excellent efficiency and unprecedented enantioselectivity.